Coordination Chemistry subproject
subproject leader: Dr. Péter Buglyó
I. Structure of the subproject
1. Bioinorganic Chemistry WG
group leader: Dr. Péter Buglyó
2. Rare Earth Metal WG
group leader: Dr. Gyula Tircsó
II. Scientific goals
- Study of the coordination chemistry of essential and toxic metal ions
- Study of coordination chemical properties of the metal ions used in medical diagnosis (Magnetic Resonance Imaging, Positron Emission Tomography, etc.) and therapy (Radioimmunotherapy).
- Synthesis and physico-chemical characterization (equilibrium, formation and dissociation kinetic studies, contrast enhancement properties) of new open-chain and macrocyclic polyamino-poly-carboxylate, -phosphonate, -phosphinate and -amidate type ligands and their complexes
- Characterization of model compounds of smart imaging agents suggested recently for molecular imaging (agents capable of binding to HSA, or sensing β-amiloid plaques, hypoxic tissue, pH and Zn2+ concentration sensitive contrast agent candidates).
- Design and synthesis of ligands for sequestering recently suggested radio isotopes like 44Sc, 52mMn, 89Zr, etc.
- Exploration of the likely role of metal ions in the development and course of certain neurodegenerative diseases (Alzheimer, Parkinson, prion disease)
- Design, synthesis and characterization of partly hypoxia-activated metal complexes with antiproliferative potential
- Study of the redox properties of essential 3d metal ion–peptide and -derivative complexes
- Design, synthesis and solution equilibrium study of the metal ion binding strengths of novel hydroxamate based chelators with potential metalloenzyme inhibition features
III. Expected results
- Development of new, more efficient metal complex based diagnostic and therapeutic agents.
- Synthesis of safer contrast agent candidates as a result of careful ligand design via tuning the physico-chemical properties of the complexes.
- Development of new of essential metal ion based intelligent/smart contrast agents for noninvasive detection of metal ions, pH, hypoxia, amyloid-plaques etc.
- A better understanding of the role of metal ions in neurodegenerative deseases by the study of metal ion binding capabilities of oligopeptides containing strongly coordinating side chains in differerent position in the peptide chain
- Development of novel, in part bimetallic, hypoxia-activated metal complexes with improved selectivity and low dose activity
- Development of new chelators for toxic metal ions (mostly for Pb(II) and Cd(II)) with improved selectivity.
IV. Infrastructure
Instruments to be purchased within the framework of the project:
- Cyclic voltammetric instrument – exploration of the redox properties of metal complexes and ligands
- pH-potentiometric titrator – study of proton dissociation and complex formation processes in solution; estimation of the stoichiometry and stability constants of the various species formed
- UV Monitoring unit for a peptide synthesizer – improvement of the yield during the synthesis of various oligopeptides, decrease of the ecological footprint
- Relaxometer –determination of the relaxation properties of metal complexes with potential use as MRI contrast agents, equilibrium and kinetic studies of the complexes of paramagnetic metal ions
- UV-VIS spectrophotometer – determination of physico-chemical properties (protonation and stability constants, formation and dissociation kinetics) of the ligands and their metal complexes